The objective was to investigate the proposition that the prostaglandin profile and its precursor pool are modulated by alcohol dose and the duration of exposure and theroby contributes to changes in the cardiovascular state. Vascular smooth muscle was either exposed to alcohol in vitro or by an inhalation technique using our automated apparatus for precise control of alcohol vapor and blood concentrations (BAC). An acute exposure to moderate alcohol levels decreases the amplitude of contraction to a thromboxane (TXA-2)-mimic, whereas higher levels do not effect the response. The observed depression in vascular contractility is associated with a significant increase in the PGI-2/TXA-2 ratio. At higher levels alcohol acts as a spasmogen, increasing intracellular Ca++ and in this way may counteract the depressive effects of prostaglandins (PG), such as prostacyclin (PGI-2) on vascular contractility. Chronic exposure to moderate BAC resulted in a mild hypertension. Furthermore, chronic alcohol inhalation significantly depressed vascular PG levels and induced a mild hyperreactivity to a thromboxanemimic. This depression in PG levels may be due in part to depletion of fatty acid substrates such as dihomogammalinolenic acid and arachidonic acid; content was inversely related to the duration of exposure and decreased by as much as 52%. Similarly, long-term exposure to high alcohol levels depressed plasma PG levels and induced a marked hyperreactivity to potent pressor agents. A high salt diet exacerbates both of these chronic alcohol effects. As expected, non-steroidal anti-inflammatory drug treatment of alcohol-naive rats induced a comparable increase in vascular reactivity to these agents. These data are consistent with the hypothesis that chronic alcohol exposure has a aspirin-like effects on the PG system as reflected by altered contractility. These effects occur only in dependent subjects (at least 3 days of alcohol exposure) and increase with the duration of exposure. Preliminary findings indicate that feeding rat dihomogammalinolenic acid partially reverses the plasma 1 and 2 series PG changes induced by alcohol.